The overall aim of this project is to identify the signals that control cell fate decisions in developing T cells. Our primarily focus for the past year has been on the role of the T cell antigen receptor (TCR) and how it works together with other developmental cues to control maturation, proliferation, death, and lineage commitment. Our progress in these areas are summarized in the following findings and conclusions: 1. The majority (1/2 to 1/3) of thymocyte precursors possessing appropriate TCRs to be selected for maturation are induced to die by negative selection. Thus, the central mechanism used to prevent autoimmunity has a profound effect on the generation of the mature T cell repertoire. 2. Distinct patterns of TCRg/d rearrangement provide evidence that the TCRab+CD4-8- and CD4/CD8 mature T cells of TCRab transgenic mice mature as separate lineages. 3. When TCRab transgenes are expressed earlier than normal, endogenous TCRg/d rearrangements are suppressed such that no T cells bearing lymphoid TCRgd appear. This suppression of rearrangement does not, however, prevent an ab/gd lineage choice. 4. Mechanisms regulating TCR gene rearrangement are distinct in the ab and gd T cell lineages. 5. Cell-cell interactions between neighboring thymocytes influence ab/gd cell fate. 6. The class of TCR expressed (ab or gd) may influence but does not work alone to specify ab or gd cell fate. Signals through the transmembrane receptor, Notch, act together with TCR signals to direct this lineage choice.